Open AccessConplastic strains for identification of retrograde effects of mitochondrial dna variation on cardiometabolic traits in the spontaneously hypertensive rat
Author(s) -
Michal Pravenec,
Jan Šilhavý,
Petr Mlejnek,
Miroslava Šimáková,
Tomáš Mráček,
Alena Pecinová,
Kateřina Tauchmannová,
M Hütl,
Hana Malínská,
Ludmila Kazdová,
Jan Neckář,
František Kolář,
Jitka Žurmanová,
Jiřı́ Novotný,
J Houštěk
Publication year - 2021
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.934740
Subject(s) - mitochondrial dna , haplogroup , biology , haplotype , genetics , human mitochondrial dna haplogroup , gene , mitochondrion , nuclear gene , phenotype , genome , transfer rna , allele , rna
Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus. Recently, natural mitochondrial genome (mtDNA) polymorphisms (haplogroups) received increasing attention in the pathophysiology of human common diseases. However, retrograde effects of mtDNA variants on such traits are difficult to study in humans. The conplastic strains represent key animal models to elucidate regulatory roles of mtDNA haplogroups on defined nuclear genome background. To analyze the relationship between mtDNA variants and cardiometabolic traits, we derived a set of rat conplastic strains (SHR-mtBN, SHR-mtF344 and SHR-mtLEW), harboring all major mtDNA haplotypes present in common inbred strains on the nuclear background of the spontaneously hypertensive rat (SHR). The BN, F344 and LEW mtDNA differ from the SHR in multiple amino acid substitutions in protein coding genes and also in variants of tRNA and rRNA genes. Different mtDNA haplotypes were found to predispose to various sets of cardiometabolic phenotypes which provided evidence for significant retrograde effects of mtDNA in the SHR. In the future, these animals could be used to decipher individual biochemical components involved in the retrograde signaling.